Descripción del proyecto
Nichos de células madre para la salud ósea
Las células madre son células especializadas capaces de producir todos los tipos celulares de un tejido u órgano y, de esa forma, contribuir a su mantenimiento y reparación. El equipo del proyecto MERLIN, financiado por el Consejo Europeo de Investigación, investiga las células madre óseas y el efecto de la alteración del nicho donde residen las células madre debido al envejecimiento o las lesiones. Aprovechando la identificación previa de un nuevo tipo de célula nicho óseo, el objetivo del proyecto es estudiar el perfil metabólico de estas células y la regulación de sus vías metabólicas. Los hallazgos del proyecto pueden conducir al desarrollo de intervenciones basadas en células madre que mejoren la salud ósea.
Objetivo
"The continued health of many of our organs, including the skeleton, relies on the function of specialized stem cells. These stem cells reside in niches that support their long-term maintenance. Disruption of the niche due to aging, injury, or genetic mutations, can lead to declines in stem cells and a failure to maintain and repair tissues. Compared to our understanding of the stem cells that maintain and repair our skeleton, we know much less about the cell types that constitute their niche. My prior large-scale genomics studies have uncovered a novel niche cell type for the skeleton. Intriguingly, these niche cells are defined by a unique metabolic profile, highlighting in particular enzymes for Phenylalanine (Phe) / Tyrosine (Tyr) metabolism and glycogen synthesis. Traditionally, it has been thought that Phe/Tyr are degraded primarily in the liver, and the skeletal malformations in patients with Phenylketonuria (mutation in PAH), Tyrosinemia (I-III, mutations in FAH, TAT, HPD) and Alkaptonuria, a.k.a. ""black bone disease"" (mutation in HGD) has been interpreted as the results of systemic intoxication by accumulated metabolites. My dogma-shattering result suggests that local regulation of Phe/Tyr degradation might be a critical strategy to support the skeleton. I will establish a research group that leverages the powerful genomic, genetic, and high-resolution imaging strengths of zebrafish to test the requirements of niche cells in skeletal stem cells homeostasis and the roles of metabolism in stem cell maintenance. Findings from my proposed studies will inform future therapies aimed at correcting metabolic diseases and restoring stem cell function and skeletal health by modulating the niche."
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
601 77 Brno
Chequia